Poly-l-lysine, with 40% of its amino groups substituted with lactose, is an effective vector to transfer the CFTR gene into CF airway epithelial cells and correct the chloride channel dysfunction. The intracellular fate of the lactosylated poly-l-lysine/cDNA complex was studied using confocal microscopy. In the presence of chloroquine the complex remained intact during internalization, intracellular transport, and, most importantly, transport into the nucleus. When cells were transfected in the presence of agents that enhance transfection efficiency such as E5CA peptide, a fusogenic peptide, or glycerol a similar fate of the lactosylated poly-l-lysine/cDNA complex was seen. However, when these agents were omitted from the transfection medium, the complex remained in the perinuclear region. Uncomplexed lactosylated poly-l-lysine reached the nucleus efficiently. In contrast mannosylated poly-l-lysine or unsubstituted poly-l-lysine complexed to plasmid did not. Therefore the nuclear accumulation of the complex may be attributed to the substitution of poly-l-lysine with lactose. It is hypothesized that the lactose residues provide for nuclear localization by means of targeting a potential lectin-like protein with galactose/lactose specificity. This mechanism may be responsible for the nuclear internalization of the complex.
Cervical spinal cord injuries may occur with catastrophic sequelae (e.g. quadriplegia) in collision sport activities. The discovery was made that the head-down tackling technique in football straightens the spine into a position vulnerable for compression and, thus, is responsible for these incidents. This led to rule changes requiring head-up tackling, which in turn resulted in the reduction of the incidence of these injuries. However, the dramatic initial reduction in the occurrence - from 32 and 34 catastrophic injuries in 1975 and 1976, respectively, down to 12 in 1977 - has levelled off with ten and eight reported cases in 2006 and 2007, respectively. The football community has increased their efforts to prevent head-down tackling with additional rule changes. Brachial plexus injury prevention must rely on properly fitted shoulder pads and use of equipment such as 'cowboy' collars. Furthermore, physicians must take into consideration cervical cord neurapraxia, congenital stenosis and other risk factors in patients who wish to return to contact sports.
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